For rational development and use of antineoplastic drugs we need to know their biochemical effects on cells and the relation of those effects to cell survival. This study was designed to study the relation between cytotoxicity and the biochemical effects of the carbamoylating activity present in some nitrosoureas. Cell cultures exposed to weakly carbamoylating or strongly carbamoylating nitrosoureas are being compared for patterns of inhibition of macromolecular synthesis, inhibition of RNA processing, and inhibition of DNA repair (all effects which can be produced by breakdown products of strongly carbamoylating nitrosoureas). The relation between these potentially lethal biochemical effects and cytotoxicity (assessed by soft-agar cloning efficiency) is being examined. To see whether carbamoylating activity may be responsible for the reported synergism between conventional alkylating agents and nitrosoureas, a comparison is being made between strongly and weakly carbamoylating nitrosoureas for their ability to produce more-than-additive cytotoxicity when used with a conventional alkylating agent. Carbamoylating could be an important source of unwanted host toxicity. But if carbamoylating activity augments antitumor activity there could be an advantage in designing nirosoureas that would generate carbamoylating compounds (isocyanates) that had some selectivity in their reactions with proteins. BIBLIOGRAPHIC REFERENCE: Fornace, A.J., Jr., Kohn, K.W., and Kann, H.E., Jr. DNA Single-Strand Breaks During Repair of UV Damage in Human Fibroblasts and Abnormalities of Repair In Xeroderma Pigmentosum. Proc. Nat. Acad. Sci. USA 73:39-43, 1976.